This study compared the efficacy of therapeutic anticoagulation guided by anti-Xa levels vs. a D-dimer-based protocol in ICU patients with COVID-19. Given the heightened risk of thrombosis despite anticoagulation therapy in some cases, we hypothesised that anti-Xa measurement improves anticoagulation effectiveness and clinical outcomes in this population. We retrospectively analysed data from ICU patients at COVID Hospital Karaburma between April 2020 and December 2021. The primary outcome was the incidence of failed noninvasive ventilation necessitating intubation. Secondary endpoints included mortality rates, thromboembolic and bleeding complications, and anticoagulation effectiveness assessed by antifactor Xa activity. The analysis included 395 patients - 137 in the anti-Xa group and 258 in the D-dimer group. The D-dimer group showed a higher rate of failed noninvasive ventilation requiring intubation (65.7% vs. 50%, P = 0.009). The overall mortality was 48.3%, significantly higher in the D-dimer group (52.7%) compared to the anti-Xa group (40.1%, P = 0.02). Thromboembolic complications were lower in the anti-Xa group (2.9%) than in the D-dimer group (9.7%, P = 0.014), with no significant difference in bleeding. Following the first LMWH administration, 70.8% of patients had anti-Xa levels below the therapeutic and 11.7% below the prophylactic range. Anti-Xa-guided anticoagulation improves survival and reduces thromboembolic complications compared to D-dimer-based treatment without increasing bleeding risk. This study highlights the potential of the anti-Xa assay in managing anticoagulation in critically ill COVID-19 patients. Our findings provide a foundation for future research on using anti-Xa measurements as a guiding tool to optimise anticoagulation therapy in other critically ill populations.

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